Personalized multidisciplinary cancer therapy

Abstract

Disclosed are assessment means, treatment protocols and compositions of matter for the personalized therapy of neoplastic malignancy. In one embodiment a patient is assessed for various body and cancer parameters and a multistep approach is undertaken which addresses: a) hormonal abnormalities; b) tumor genetic composition; c) immunological status of the tumor; d) nutrient deficiencies; e) oxidative stress associated with the tumor; and f) tumor acidity. Subsequent and/or concurrent with addressing abnormalities various therapeutic interventions are utilized including immunotherapy, chemotherapy, radiotherapy and metabolic therapy. Immunization means are also provided to prevent the possibility of tumor relapse.

1 . A method of treating cancer comprising: a) examining a cancer patient for tumor and host associated abnormalities; b) addressing said abnormalities; c) providing one or more therapeutic interventions; and d) providing immunological support to avoid tumor recurrence. 
     
     
         2 . The method of  claim 1 , wherein said therapeutic capable of reducing tumor-associated immune suppression is an antioxidant selected from the group comprising of: a) n-acetylcysteine; b) intravenous ascorbic acid; c) pterostilbene; d) vitamin k3; e) resveratrol; f) alpha lipoic acid; g) quercetin; h) kaempferol; i) myricetin; j) apigenin; k) luteolin; l) curcumin; and m) caffeic acid. 
     
     
         3 . The method of  claim 1 , wherein said therapeutic capable of reducing tumor-associated immune suppression is a phosphodiesterase (PDE)-5 inhibitor, wherein said PDE-5 inhibitor is selected from a group comprising of: a) Acetildenafi; b) Aildenafil; c) Avanafil; d) Benzamidenafil; e) Homosildenafil; f) Icariin; g) Lodenafil; h) Mirodenafil; i) Nitrosoprodenafil; j) Sildenafil; k) Sulfoaildenafil; l) Tadalafil; m) Udenafil; n) Vardenafil; and o) Zaprinast. 
     
     
         4 . The method of  claim 1 , wherein said therapeutic capable of reducing tumor-associated immune suppression is an agent capable of reducing VEGF, wherein said agent capable of reducing said VEGF is selected from a group comprising of: a) Avastin; b) Ciclopirox; c) penicillamine; d) tetrathiomolybdate; e) fish oil; f) selenium; g) green tea polyphenols; h) glycine; i) zinc; j) cirsimaritin; k) Eupafolin; l) Andrographolide; m) Procyanidin B2; n) Procyanidin B3; o) 6-O-angeloylenolin; p) Cyperenoic acid; q) Penduliflaworosin; r) Tylophorine; s) Ellagic acid; t) brucine; u) Punarnavine; v) Raddeanin A; w) Platycodin D; x) withanone; y) 4-Hydroxyphenylacetic acid; z) trans-ethyl p-methoxycinnamate; aa) Decursin; ab) decursinol angelate; and ac) Artesunate. 
     
     
         5 . The method of  claim 1 , wherein said therapeutic capable of reducing tumor-associated immune suppression is a checkpoint inhibitor, wherein said checkpoint inhibitor is an agent capable of blocking molecules selected from a group comprising of: a) PD-1; b) PD-Li; c) CTLA-4; d) LAG-3; e) TIGIT; f) KIR; g) indolamine 2,3 deoxygenase; h) NR2F6; i) TIM-3; j) ILT-3; and k) GITR. 
     
     
         6 . The method of  claim 1 , wherein said patient is immunized with a tumor antigen, wherein said tumor antigen possesses similarity to said tumor which said patient is afflicted by. 
     
     
         7 . The method of  claim 6 , wherein said tumor antigen is derived from a histologically similar tumor to which said patient is afflicted with. 
     
     
         8 . The method of  claim 7 , wherein said tumor antigen is derived by lysis of histologically similar tumors. 
     
     
         9 . The method of  claim 7 , wherein said tumor antigen is derived by mRNA extraction of histologically similar tumors. 
     
     
         10 . The method of  claim 7 , wherein said tumor antigen is derived by exosome extraction of histologically similar tumors. 
     
     
         11 . The method of  claim 6 , wherein said tumor antigen is a tumor associated antigen. 
     
     
         12 . The method of  claim 11 , wherein said tumor associated antigen is selected from a group comprising of: a) Fos-related antigen 1; b) LCK; c) FAP; d) VEGFR2; e) NA17; f) PDGFR-beta; g) PAP; h) MAD-CT-2; i) Tie-2; j) PSA; k) protamine 2; l) legumain; m) endosialin; n) prostate stem cell antigen; o)carbonic anhydrase IX; p) STn; q) Page4; r) proteinase 3; s) GM3 ganglioside; t) tyrosinase; u) MART1; v) gp100; w) SART3; x) RGS5; y) SSX2; z) Globol1; aa) Tn; ab) CEA; ac) hCG; ad) PRAME; ae) XAGE-1; af) AKAP-4; ag) TRP-2; ah) B7H3; ai) sperm fibrous sheath protein; aj) CYP1B1; ak) HMWMAA; al) sLe(a); am) MAGE A1; an) GD2; ao) PSMA; ap) mesothelin; aq) fucosyl GM1; ar) GD3; as) sperm protein 17; at) NY-ESO-1; au) PAX5; av) AFP; aw) polysialic acid; ax) EpCAM; ay) MAGE-A3; az) mutant p53; ba) ras; bb) mutant ras; bc) NY-BR1; bd) PAX3; be) HER2/neu; bf) OY-TES1; bg) HPV E6 E7; bh) PLAC1; bi) hTERT; bj) BORIS; bk) ML-IAP; bl) idiotype of b cell lymphoma or multiple myeloma; bm) EphA2; bn) EGFRvIII; bo) cyclin B1; bp) RhoC; bq) androgen receptor; br) surviving; bs) MYCN; bt) wildtype p53; bu) LMP2; by) ETV6-AML; bw) MUC1; bx) BCR-ABL; by) ALK; bz) WT1; ca) ERG (TMPRSS2 ETS fusion gene); cb) sarcoma translocation breakpoint; cc) STEAP; cd) OFA/iLRP; and ce) Chondroitin sulfate proteoglycan 4 (CSPG4). 
     
     
         13 . The method of  claim 12 , wherein a peptide or plurality of peptides derived from said antigens are used for immunization. 
     
     
         14 . The method of  claim 13 , wherein said peptides used for immunization are matched with HLA haplotype of said patient in need of therapy. 
     
     
         15 . The method of  claim 13 , wherein said peptides are altered peptide ligands. 
     
     
         16 . The method of  claim 11 , wherein said immunization with said tumor antigen is performed together with an adjuvant. 
     
     
         17 . The method of  claim 16 , wherein said adjuvant is a stimulator of antigen presentation. 
     
     
         18 . The method of  claim 17 , wherein said stimulator of antigen presentation is a toll like receptor (TLR). 
     
     
         19 . The method of  claim 18 , wherein said toll like receptor is activated by peptide possessing at least 80 percent homology to the sequence (SEQ ID NO: 1) EFDVILKAAGANKVAVIKAVRGATGLGLKEAKDLVESAPAALKEGVSKDDAEALKKAL EEAGAEVEVK. 
     
     
         20 . The method of  claim 18 , wherein said TLR is activated by High mobility group box 1 (HMGB-1) protein.